Molecular Dynamics Simulation of Human Pancreatic Lipase and Lipase-colipase Complex: Insight into the Structural Fluctuations and Conformational Changes
International Journal of Computational and Theoretical Chemistry
Volume 8, Issue 1, June 2020, Pages: 19-26
Received: Jan. 25, 2020;
Accepted: Feb. 17, 2020;
Published: Feb. 28, 2020
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Sikiru Akinyeye Ahmed, Department of Chemistry, Kwara State University, Malete, Ilorin, Nigeria
Nizakat Ali, International Centre for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, Pakistan
Urooj Qureshi, International Centre for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, Pakistan
Ruqaiya Khalil, International Centre for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, Pakistan
Zaheer-Ul Haq Qasmi, International Centre for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, Pakistan
Although the structure of Human Pancreatic Lipase has been documented through the X-ray crystallography, the knowledge about the molecular rearrangement and dynamic equilibrium in the structure (particularly in the catalytic triad and lid domains) is very scanty. The structural fluctuations and conformational changes undergo by Human Pancreatic Lipase (HPL) with and without colipase were computationally investigated through molecular dynamics simulation technique using GROMACS 2018.4, MOE 2016.0801 and VMD softwares in order to gain insight into the complex transitions at different domains. The structural stability was revealed vis-a-vis Root Mean Square Deviation (RMSD) and Root Mean Square Fluctuations (RMSF) plots. The levels of compactness/folding and conformational changes of the protein were determined using Radius of gyration and secondary analysis respectively. Salt bridge analysis gives more ionic pairs interactions than experimentally determined results. Results show that though both proteins are stable, lipase-colipase complex is more deviated and flexible than lipase. Also, additional information regarding the conformational transitions, interactions and dynamics that govern stability of lipase-colipase complex which were ‘hidden’ to experimental techniques were revealed.
Sikiru Akinyeye Ahmed,
Zaheer-Ul Haq Qasmi,
Molecular Dynamics Simulation of Human Pancreatic Lipase and Lipase-colipase Complex: Insight into the Structural Fluctuations and Conformational Changes, International Journal of Computational and Theoretical Chemistry.
Vol. 8, No. 1,
2020, pp. 19-26.
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